The present invention relates to devices for the metering of small quantities of powder from fluidized beds through a volumetric measuring device.
Accurate metering of a given quantity of powder is often required in various processes including chemical engineering and pharmaceutical processes. When the metered quantity is large, this is relatively easily achieved. However, when the required quantity is very small, this becomes very difficult if high accuracy is required at the same time. In addition, if very fine powder is used, strong interparticle forces cause the powder to agglomerate, thus making the precise metering even more difficult.
Pulmonary drug delivery represents a new drug administration method that provides many advantages. It provides direct and fast topical treatments to respiratory and lung diseases. It has less first-pass GI (gastrointestinal) metabolism and can provide targeted delivery to heart and brain. Drugs such as peptides can be systemically delivered using the pulmonary channel. Pulmonary drug delivery also allows the use of drugs with low solubility. Antibiotics and even vaccines can be delivered in this manner. Compared to oral in-take, it provides a fast and much more efficient adsorption. Typically, only a few percent of the medication of the oral in-take is required for pulmonary delivery. Compared to intravenous injection, it provides a painless and safe alternative.
To facilitate pulmonary delivery, drug powders should normally be less than 5 xcexcm so that they become airborne during inhalation. However, powders of such small sizes (typical group C powder in the Geldart classification) have very strong interparticle forces that make them agglomerate and cohesive, and thus very difficult to handle. Since the required dosage for pulmonary delivery is also very small (usually in the order of 1 xcexcg-100 mg), this makes it very difficult to accurately meter such a small quantity and fill them into packages.
To overcome the interparticle forces, current industrial practice applies two different methods; one involves mixing the ultrafine drug powders with large amounts of coarser powder, and the other the suspension of the powder in liquid. The first method uses a large quantity of excipient (filler) particles that are much larger (normally group A or group A-C powders in the Geldart classification). This makes the small-large powder mixture fluidize and flow easily so that they can be handled more easily. It also significantly increases the volume of each dosage so that the dispensing becomes more accurate when the drug powder is packaged into the Dry Powder Inhaler (DPI). However, only a small fraction of the small drug particles can detach effectively from the large excipient particles during inhalation and the rest stay with the large particles and land in the mouth, limiting the efficiency of final delivery to about 10-15%.
The second method involves suspending the ultrafine drug powders into liquids such as hydrocarbon propellants and storing them in Metered Dose Inhalers (MDI). When a metered quantity of the propellant is released from the storage canister, the propellant evaporates and expands quickly to disperse the powdered drug into the patients"" mouth. The key problem with this method is that the quick expansion of the propellant causes the drug to impact in the back of the throat and other places in the mouth, reducing the amount being inhaled into the lung to less than 10-15%. This method also needs good breath coordination, since it is difficult to predict the amount of drug inhaled if the patients"" inhalation does not coincide with the drug releasing.
Thus both currently practiced methods have significant limitations. It would be ideal if the required small quantity of the fine drug powder could be accurately dispensed alone, without any other chemical or physical constituents. When only the pure drug powder is packaged into the inhaler, the delivery efficiency is expected to increase significantly. However, this tends to be fairly difficult if the quantity to be packaged is extremely small. For example, if each dose contains 0.5 mg or 500 xcexcg of drug powder and the bulk (packed) density of the powder is 0.5 mg/mm3(=500 kg/m3), the total volume of the powder withdrawn for each dose is only 1.0 mm3.
Fluidization occurs when particulate materials of sub-micrometers to several millimeters are suspended by up-flowing gas in a vessel or column to form a gas-solid suspension more commonly referred to as a fluidized bed. The fluidized beds formed with the gas-solid suspension are specifically referred to as gas-solid fluidized beds. The term xe2x80x9cfluidized bedxe2x80x9d applies because the gas-solid suspension formed by the solid particles and the upflowing gas behaves like a fluid. Although primarily gas is used as fluidizing fluid, liquid can also be used. In some cases, both gas and liquid are used together. Those are called liquid-solid fluidized beds and gas-liquid-solid three-phase fluidized beds.
A gas-solid fluidized bed can operate in several fluidization regimes: particulate, bubbling, slugging and turbulent fluidization regimes (conventional fluidized beds), and fast fluidization and pneumatic transport regimes (high-velocity fluidized beds). In a conventional fluidized bed, there are usually two distinct regions: the upper dilute region (also called the freeboard region) and the bottom dense region which has most of the particles and also contains many more particles per volume than the dilute region. In a high-velocity fluidized bed, almost all particles are carried upwards by the high-velocity upflow gas and almost the entire bed is in a dilute suspension region. There is also a downflow fluidization regime where gas and particles flow co-currently downward in a dilute suspension form.
A typical design of a fluidized bed includes a gas distributor at the bottom of the fluidized bed column, the main function of which is to uniformly distribute the gas into the fluidized bed. The vessel that contains the fluidized bed can have any suitable shape, but those with cylindrical or rectangular cross-sections and oriented on a substantially vertical axis are commonly used. The vertical walls are usually of solid materials to prevent the gas and solids from escaping from the fluidized beds.
Sometimes, it is necessary to have solid feeds and withdrawal ports and/or heat transfer tubes or panels mounted on the wall(s) of a fluidized bed. At the top of the bed, there is usually a plate or similar structure that seals the top of the fluidization column. There is usually at least one exit port through the top plate and/or the side wall not far below the top plate that allow gas and entrained solids to leave the fluidized bed and enter into gas-solid separation devices or other vessels or other process units. Those particles that leave the fluidized bed are entrained out by the gas flow, i.e. by solids entrainment.
Powders may be classified into four groups in gas-solid fluidized systems, according to Geldart""s classifications. Groups B and D powders comprise large particles that typically result in large bubbles when fluidized. Group A powders comprise particles that first experience a significant expansion of the powder bed when fluidized before bubbles begin to appear. Group C powders comprise very small particles for which the interparticle forces significantly affect the fluidization behaviour. As the particle size reduces, interparticle forces increase significantly. Those strong interparticle forces cause the fine particles to agglomerate and make them very cohesive. Typical Group C powders comprise particles under 30-45 xcexcm in size, although some very sticky powders larger than these sizes may also belong to Group C powders. Due to strong interparticle forces, Group C powders are either very difficult to fluidize (with channeling and/or very poor fluidization) or mainly fluidize with the large agglomerates as pseudo-particles rather than as individual particles. In either case, fluidization of individual particles cannot be achieved easily so that handling of Group C powders becomes a difficult problem.
Different measures can be taken to assist the fluidization of Group C powders. Those methods are usually referred to as fluidization aids. Fluidization aids include mechanical stirring, mechanical, acoustic or ultrasonic vibration, addition of much larger particles or other objects to provide extra stirring, addition of finer particles to act as xe2x80x9clubricantxe2x80x9d, pulsation of fluidization gas, etc. Some aids are more effective than others for a given Group C powder, but the effectiveness of almost all aids tends to diminish as the powder becomes finer.
Group C powders also tend to clog up in certain areas of the fluidized bed, such as above the gas distributor, around internals and at exit port(s), and to stick to the internal wall or the ceiling of the bed. Large chunks of powder form in those places and then break from time to time as they grow and become unstable. As those chunks of particles from the ceiling or upper portion of the bed fall back into the fluidized bed, they disturb the flow hydrodynamics inside the bed, causing periodical variation of the bed density and other properties in both the bottom dense phase region and the upper dilute phase region.
Key characteristics of fluidized beds include easy handling of particles, excellent contact between gas and solids, excellent heat and mass transfer between gas and solids and between gas-solid suspensions and the column wall, good gas and solids mixing, etc. These and other useful characteristics have led to the wide application of fluidized beds in process and other industries. The xe2x80x9ceasy handling of particlesxe2x80x9d is due to the uniform solids suspension inside the bed and the relatively free movement of the particles within the gas-solids suspension and of the suspension itself.
Several well known problems currently exist with the fluidized beds pertaining to the metering of fine particles, especially Group C particles. Solids entrainment can sometimes cause problems to the maintenance of a uniform suspension, since entrained particles may flow out of the fluidized bed with the gas stream from the top exit. In order to maintain a constant suspension, escaped particles must be separated from the gas stream (by cyclone, bag filter and/or other devices) and returned. Because there is limitation on the separation efficiency, some particles may be lost even with several stages of separation, leading to a reduction of the powder inventory. This presents a serious problem in some cases where it is essential not to lose particles, such as in the case where expensive drug powder is handled. In this case, a filter may be installed inside or just at the exit port to stop the entrained particles from flowing out of the bed in the first place. However, such filters are plugged very quickly that periodical purging is essential. In addition, such filters also produce a high pressure drop that a very large filter area has to be created to allow enough gas to flow through.
The main problem associated with particle loss and with the gradual decrease of solids inventory due to continuous metering out of particles, is the reduction of solids suspension density. Such variations in solids suspension density may reduce the accuracy of powder metering from the fluidized bed. One measure is to continuously add additional particles into the fluidization column. An alternative measure proposed in this invention and discussed hereinafter is to gradually decrease the volume of the fluidized bed by moving one or more side of the column wall inwards.
Another problem with fluidized beds is that local dead zones or defluidization may occur due to the non-uniform gas distribution at the bottom or due to other reasons such as agglomeration of fine or ultrafine (Group C) particles. This can result in non-uniform and unpredictable suspension density, and other undesirable consequences. For greater certainty, particle agglomeration happens when very fine powder, such as the drug powder for pulmonary drug delivery, is fluidized. Such agglomeration causes non-uniform solids suspension and solids flow, greatly reducing the accuracy of powder metering from the fluidized bed.
Yet another problem is that some particles tend to stick on the inner wall or the top plate of the fluidization vessel/column. This is especially true when very fine particles are fluidized. This can lead to unwanted solids accumulation on the wall. Accumulation of particles on the wall reduces the solids holdup (=concentration) in the bed, making it difficult to precisely control the fluidized bed density, as desired in some processes. Those particles stuck on the wall may also fall periodically back to the bed (for example, when the accumulation is too thick), changing suddenly the bed density, that is, the solids concentration in the bed. A rotating fluidized bed can be used to overcome this problem. The concept of rotating fluidized bed with porous walls is known, however such beds are rotated to generate centrifugal force to the particles in the bed and are known as centrifugal fluidized beds. In these devices, the cylindrical wall is porous. The porous wall is used as gas distributor for the fluidizing gas to flow inward in all radial directions into the bed and the gas exits through the axial end(s) of the cylinder. The purpose of rotating the cylindrical (horizontal or vertical) vessel is to create a centrifugal force to hold the particles towards the cylindrical wall so that higher fluidization velocity can be used without producing large bubbles in the bed and/or without having significant solids entrainment. This allows the same bed to be operated at higher gas velocity so that the process capacity is increased. Example references that provide the details of such rotating fluidized beds include R Pfeffer, G I Tardos and E Gal, xe2x80x9cThe use of a rotating fluidized bed as a high efficiency dust filterxe2x80x9d, in Fluidization V, eds., K. Ostergaard and A. Sorensen, Eng. Foundation, New York, pages 667-672, 1986; J. Kao, R Pfeffer and G I Tardos, xe2x80x9cOn partial fluidization in rotating fluidized bedsxe2x80x9d, American Institute of Chemical Engineering Journal, Volume 33, pages 858-861, 1987; Qian G-H, I Bagyi, R Pfeffer, H Shaw and J G Stevens, xe2x80x9cA parametric study on a horizontal rotating fluidized bed using slotted and sintered metal cylindrical gas distributorsxe2x80x9d, Powder Technology, Volume 100, pages 190-199, 1998; Qian G-H, I Bagyi, R Pfeffer and H Shaw, xe2x80x9cParticle mixing in rotating fluidized beds: inferences about the fluidized state xe2x80x9d, American Institute of Chemical Engineering Journal, Volume 45, pages 1401-1410, 1999; and U.S. Pat. No. 6,197,369.
However, the key design concepts and the purpose of such prior art centrifugal fluidized beds are significantly different from the rotating and porous fluidized bed dispenser proposed in this invention.
U.S. Pat. No. 5,826,633 issued to Parks et al. is directed to a powder filling apparatus which uses gravity to assist filling of a metered chamber. The metered chamber is placed below a convergent passageway containing the powder that is being dispensed. While the method and device involves xe2x80x9cfluidizingxe2x80x9d the powder to overcome inter-particle cohesive forces, they defined fluidizing powder as xe2x80x9cthe powder is broken down into small agglomerates and/or completely broken down into its constituents or individual particlesxe2x80x9d. In their definition, upflowing gas is not essential to cause the powder to be fluidized. This is significantly different from the conventional definition of fluidization, as followed in this patent application, that powder is fluidized when it is suspended in an upflowing gas (or liquid). As a result, the device is not per se a fluidized bed since in this device all particles fall unassisted by gravity. In conventional fluidized beds particles are suspended by the fluidizing gas and very few, if any, particles can fall unassisted by gravity. Further, some typical components of a fluidized bed such as an air distributor is missing in this device. In addition, other problems as described above in this invention, such as sticking of particles to the inner surface of the convergent chamber is still problematic with this type of device.
U.S. Pat. No. 6,183,169 issued to Zhu et al. is directed to a device for precision dispensing of fine powders. This device includes two fluidized bed chambers communicating with each other and operates by first fluidizing a fine powder in one chamber and then using a pressure differential between the chambers to draw the fluidized particles into the second chamber. A solenoid valve attached to the second chamber is opened for a selected period of time to dispense the powder in the form of gas-solid suspension to a collection area. The two-chamber concept utilized by Zhu et al. in U.S. Pat. No. 6,183,169 is different from the one used in the current invention. It uses a two-stage method to dilute and control the gas-solids suspension and a Venturi mechanism to control the powder flow and to transport the powder from one stage to another, while the current invention only has one stage and does not require a Venturi or anything of such kind to control powder flow. In the device disclosed in Zhu et al. powder withdrawal is from the dilute phase in the second chamber.
Obviously, the key concepts of both U.S. Pat. Nos. 5,826,633 and 6,183,169 are different from the current invention.
In view of the difficulties and complexities with the prior art, it would be advantageous to provide a single fluidized bed which can dispense quantities of fine powder in an accurate and controlled manner which can be used for either batch or continuous processing of the fine powders. It would also be very advantageous to provide a fluidized bed system that significantly reduces solids accumulation on the walls of the fluidized bed, achieves total solids containment in the bed except for targeted particle withdrawal through selected ports, reduces or eliminates dead zones, and/or allows for the addition and removal of gas at various locations in the fluidized bed.
This invention utilizes the uniform solids suspension and easy mobility of particles inside the fluidized bed, from which particles are uniformly withdrawn to a fixed-volume cavity so that a definite quantity of particles can be metered out from the fluidized bed. To ensure consistency and accuracy of such powder metering, it is essential to maintain a constant and consistent gas-solids suspension inside the fluidized bed.
The method disclosed herein involves metering the powder flow from a fluidized bed where the particle suspension has a much lower density than that of packed (bulk) particles so that the withdrawal volume is significantly increased to increase metering accuracy, and where the particles are completely mobile so that a consistent withdrawal can be maintained.
The present invention also discloses rotating the porous fluidized bed to alternately switch the gas distributor, the bed wall and/or the top gas exit plate, so that particles stuck onto the wall can be continuously back purged off the wall when they are rotated to the bottom of the bed where the gas is introduced in the bed.
The current invention proposes the following alternatives to provide further agitation to the powder to enhance uniform fluidization: (1) rotating the fluidized bed, with or without adding large beads in the bed; (2) injecting additional gas into the bed at various locations in the bed through gas nozzles; and (3) using gas nozzles with flexible tube that can move randomly inside the bed.
An object of the present invention is to provide accurate volumetric metering of powder, either by filling a receptacle of given volume or by timing the powder flow at a given volumetric flow-rate, from a fluidized bed. In particular, this invention addresses the problems associated with metering of extremely small quantities (1 xcexcg-100 mg) of ultrafine ( less than 10 xcexcm) powders. To ensure precise metering, the invention provides fluidized bed structures that intend to ensure uniform and relatively constant gas-solids suspension inside the fluidized bed, by minimizing the problems associated with maintaining uniform gas-solids suspension and uniform fluidization. This invention also provides effective means to volumetrically meter and withdraw the required small quantities of powder in a very accurate and controlled manner.
It is a further object of the present invention to provide a fluidized system that may be used for reduction of solids accumulation on the walls, to provide a system that may be used for reduction or elimination of dead zones, and to provide a system that may be used to add and remove gas at various locations (e.g., along the axial direction).
Broadly, the present invention relates to metering a small quantity of powder from a fluidized bed using a volumetric method. It can be just any fluidized bed that can provide a steady gas-solid suspension and the withdrawal can be either from the dense phase or the dilute phase of the bed. An element of some suitable shape that has one or more cavities and that can be easily engaged and disengaged to the said fluidized bed with the cavities exposed to the fluidized bed is used for the metering and withdrawal.
Furthermore, the present invention relates to a fluidized bed structure comprising having a housing defining a fluidized bed chamber, means for introducing primary fluidizing fluid through one or more portion(s) of the surrounding walls into the chamber at one or more side(s) of the chamber and means for permitting the escape of the fluid through one or more portion(s) of the surrounding walls from the chamber at other one or more side(s) of said chamber. At least some of the walls of the chamber have a significant area that is porous, the porous area comprising pores having a size sufficiently small to prevent significant loss of particles from the fluidized bed.
This invention further relates to a powder metering and withdrawal mechanism that is attached to the fluidized bed. This mechanism includes an element of some suitable shape that has one or more small cavities (pockets, holes) and means (withdrawal port) to engage and disengage such element easily to/from the fluidized bed with the cavities exposed to the gas-solid suspension inside the fluidized bed.
In one aspect the present invention provides a fluidized bed for dispensing powders, comprising:
a) a housing defining an enclosure for containing particulate matter, said housing including a fluid injection means for injecting a fluid into said enclosure for fluidizing particulate matter contained within said housing for forming a dilute phase and a dense phase of fluidized powder in said housing; and
b) volumetric metering means connected to said housing and in flow communication with said enclosure through an outlet passageway for withdrawing pre-selected amounts of said particulate matter from said housing.
In another aspect of the invention there is provided a fluidized bed for dispensing powders, comprising:
a) a housing defining an enclosure for containing particulate matter, said housing including at least one porous wall having a suitable porosity to allow flow of fluid through said porous wall while preventing most of the particulate matter contained within said housing from passing through said porous wall, a fluid injection means for injecting a fluid into said enclosure for fluidizing particulate matter contained within said housing for forming either a dilute phase only or a dilute phase and a dense phase of fluidized powder in said housing; and
b) time controlled powder withdrawal means connected to said housing and in flow communication with said enclosure through an outlet passageway for withdrawing particulate matter from said housing for a pre-selected period of time.